Combined bioavailable isoflavones and probiotics improve bone status and estrogen metabolism in postmenopausal osteopenic women: a randomized controlled trial.
What this study found
Overall, the bioavailable red clover isoflavone plus probiotic regimen was beneficial and well tolerated, with no adverse events reported. It favorably shifted estrogen metabolism: the urinary 2-OH:16a-OH ratio increased from 2.77 ± 0.19 to 3.41 ± 0.23 in the active group, versus 3.13 ± 0.27 to 2.98 ± 0.17 in controls, with an intergroup difference of P < 0.05. Equol production also increased, with 55% (n = 21) classified as equol producers at 6 months and equol concentration reaching 39.80 ± 15.68 nmol/L versus 3.02 ± 0.67 nmol/L in controls. Bone turnover also improved, with CTx decreasing…
- Study & population
- Randomized controlled trial in postmenopausal women with osteopenia recruited from northern Denmark.
- Intervention
- Oral fermented red clover extract rich in isoflavone aglycones, given twice daily as 2 × 95 mL for 12 months, providing 60 mg isoflavone aglycones/day.
- Key limitation
- The trial was conducted in a specific group of postmenopausal osteopenic women from one region, limiting generalizability.
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Open PDFOriginal abstract
Background: Female age-related estrogen deficiency increases the risk of osteoporosis, which can be effectively treated with the use of hormone replacement therapy. However, hormone replacement therapy is demonstrated to increase cancer risk. Bioavailable isoflavones with selective estrogen receptor affinity show potential to prevent and treat osteoporosis while minimizing or eliminating carcinogenic side effects.Objective: In this study, we sought to determine the beneficial effects of a bioavailable isoflavone and probiotic treatment against postmenopausal osteopenia.Design: We used a novel red clover extract (RCE) rich in isoflavone aglycones and probiotics to concomitantly promote uptake and a favorable intestinal bacterial profile to enhance isoflavone bioavailability. This was a 12-mo, double-blind, parallel design, placebo-controlled, randomized controlled trial of 78 postmenopausal osteopenic women supplemented with calcium (1200 mg/d), magnesium (550 mg/d), and calcitriol (25 μg/d) given either RCE (60 mg isoflavone aglycones/d and probiotics) or a masked placebo [control (CON)].Results: RCE significantly attenuated bone mineral density (BMD) loss at the L2-L4 lumbar spine vertebra (P < 0.05), femoral neck (P < 0.01), and trochanter (P < 0.01) compared with CON (-0.99% and -2.2%; -1.04% and -3.05%; and -0.67% and -2.79, respectively). Plasma concentrations of collagen type 1 cross-linked C-telopeptide was significantly decreased in the RCE group (P < 0.05) compared with CON (-9.40% and -6.76%, respectively). RCE significantly elevated the plasma isoflavone concentration (P < 0.05), the urinary 2-hydroxyestrone (2-OH) to 16α-hydroxyestrone (16α-OH) ratio (P < 0.05), and equol-producer status (P < 0.05) compared with CON. RCE had no significant effect on other bone turnover biomarkers. Self-reported diet and physical activity were consistent and differences were nonsignificant between groups throughout the study. RCE was well tolerated with no adverse events.Conclusions: Twice daily RCE intake over 1 y potently attenuated BMD loss caused by estrogen deficiency, improved bone turnover, promoted a favorable estrogen metabolite profile (2-OH:16α-OH), and stimulated equol production in postmenopausal women with osteopenia. RCE intake combined with supplementation (calcium, magnesium, and calcitriol) was more effective than supplementation alone. This trial was registered at clinicaltrials.gov as NCT02174666.